Key result
Diazoxide-induced hypoinsulinemia augmented lipoprotein lipase at the coronary lumen within 4 hours, accompanied by a 50% reduction in myocyte cell surface LPL.
Hypoinsulinemia rapidly augments LPL at the coronary lumen via a mechanism involving triglyceride breakdown and Lyso-PC.
Hypothesis-generating for hypoinsulinemia effects on cardiac LPL; clinical implications remain to be determined.
OBJECTIVE: Lipoprotein lipase (LPL) mediated hydrolysis of circulating triglyceride (TG)-rich lipoproteins provides the heart with fatty acids. The present study was designed to investigate the influence of circulating TG and their lipolysis in facilitating translocation of LPL from the underlying cardiomyocyte cell surface to the coronary lumen. METHODS: The in vivo effects of diazoxide (DZ), an agent that causes rapid hypoinsulinemia, and the in vitro effect of the lipoprotein breakdown product L-alpha-lysophosphatidylcholine (Lyso-PC) on luminal LPL were examined in Wistar rats. Manipulation of circulating TG in DZ-treated animals and their influence on LPL was also determined. RESULTS: Within 4 h following DZ a major increase in LPL activity and protein occurred at the coronary lumen. Myocyte cell surface LPL was reduced 50% subsequent to DZ. Exposure of isolated control hearts to 1 nM Lyso-PC enhanced luminal LPL to levels observed following DZ. Treatment of DZ animals with either WR 1339 (inhibits circulating TG breakdown) or N(6)-cyclopentyladenosine (inhibits adipose tissue lipolysis) decreased DZ induced augmentation of cardiac LPL. CONCLUSIONS: Using DZ, our studies for the first time demonstrate that LPL at the coronary lumen can be augmented as early as 4 h after hypoinsulinemia and that this increase likely involves posttranslational processing via TG breakdown of circulating lipoproteins and a Lyso-PC dependent mechanism.
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Thomas Pulinilkunnil (2003) studied this question. Diazoxide (DZ) vs. control was evaluated on LPL activity and protein at the coronary lumen. Diazoxide-induced hypoinsulinemia augmented lipoprotein lipase at the coronary lumen within 4 hours, accompanied by a 50% reduction in myocyte cell surface LPL.
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